This Program Project Grant (PPG) will bring together 16 investigators in four Projects and two Cores to continue our work in the area of the link between chronic infection (M. pneumoniae) and chronic asthma. There have been numerous recent publications suggesting that in a subgroup of asthmatics, approximately 50% have an associated atypical bacterial process. Thus, this PPG will focus on the M. pnemoniae-asthma interaction. Project 1 will evaluate the effect of M. pneumoniae on neurogenic inflammation inducing fibroblast proliferation and altering airway structure (remodeling) and function. This will be done using asthmatic airway epithelial cells and tissue. The focus of Project 2 is to examine the interactions of surfactant proteins (SP)-A and -D, the first line airway defense mechanisms and M. pneumoniae. This project will also identify the domains of the protein that are required for the amplification of the inflammatory response. In addition to this in vitro work, in vivo mouse work will determine how the mycoplasma response is modulated by SP-A and SP-D. Project 3 will use a mouse model of a mycoplasma induced chronic "asthma-like" state by the interaction of allergen and infection exposures. This model will be used to understand the development of chronic bronchial hyper-responsiveness and airway remodeling. Project 4 will use an epithelial human cell line to investigate the effects of M. pneumoniae on mast cell function. Each project is complementary and interactive, thus the critical mass of scientists will be able to work at a higher and interactive level through the PPG. The Administrative Core will function as the fulcrum for the projects and the Histopathology and Microbiology Core will serve each project. The goal of understanding the interaction between M. pneumoniae and asthma will be obtained through this PPG and will ultimately give new knowledge to the understanding of asthma pathophysiology and potential future novel therapies.